Chinese Journal of Organic Chemistry >
Synthesis and Biological Activity of Novel 1,3,4-Thiadiazole Thioether Derivatives Containing Pyrimidine Moiety
Received date: 2016-10-17
Revised date: 2016-12-20
Online published: 2017-01-17
Supported by
Project supported by the National Natural Science Foundation of China (No. 30900959) and the Public Project of Zhejiang Province (No. 2014C31127).
In order to find novel biologically active heterocyclic compounds, fifteen novel 1,3,4-thiadiazole thioether derivatives carrying pyrimidine moiety were prepared by using thiocarbamide and 2,4-pentanedione as the staring materials via cyclization, etherification, hydrazination, cyclization and the last benzylation reaction under microwave irradiation. The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR, IR, ESI-MS and elemental analysis. The preliminary bioassay results indicated that some target compounds exhibited moderate inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 μg/mL, and the inhibition rate of 2-(((4,6- dimethylpyrimidin-2-yl)thio)methyl)-5-((3-fluorobenzyl)thio)-1,3,4-thiadiazole (7i) against Colletrotichum acutatum and Colletrotichum fragariae were 79.84% and 73.46% respectively. Several compounds also showed good antileishmanial activities against Leishmania donovani, 2-(((4,6-dimethylpyrimidin-2-yl)thio)methyl)-5-((2-fluorobenzyl)thio)-1,3,4-thiadiazole (7h) and 2-(((4,6-dimethylpyrimidin-2-yl)thio)methyl)-5-((4-fluorobenzyl)thio)-1,3,4-thiadiazole (7j) were found highly active with IC50 values of 21.3 and 23.6 μg/mL, respectively.
Li Qianmei , Pang Kaisheng , Zhao Jianping , Liu Xinghai , Weng Jianquan . Synthesis and Biological Activity of Novel 1,3,4-Thiadiazole Thioether Derivatives Containing Pyrimidine Moiety[J]. Chinese Journal of Organic Chemistry, 2017 , 37(4) : 1009 -1015 . DOI: 10.6023/cjoc201610026
[1] Chen, S.-Z. M.S. Thesis, Northwest University, Xi'an, 2008 (in Chinese).
(陈书哲, 硕士论文, 西北大学, 西安, 2008. )
[2] Kumar, D.; Kumar, N. M.; Noel, B.; Kavita, S. Eur. J. Med. Chem. 2012, 55, 432.
[3] Wang, T.-T.; Miao, W.-K.; Wu, S.-S.; Bing, G.-F.; Zhang, X.; Qin, Z.-F.; Yu, H.-B.; Qin, X.; Fang, J.-X. Chin. J. Chem. 2011, 29, 959.
[4] Han, F.; Wan, R.; Wang, Y.; Wang, P.; Wang, J.-T. Chin. J. Org. Chem. 2010, 30, 132 (in Chinese).
(韩峰, 万嵘, 王瑶, 王朋, 王锦堂, 有机化学, 2010, 30, 132.)
[5] Zou, X.-J.; Lai, L.-H.; Jin, G.-Y.; Zhang, Z.-X. J. Argic. Food Chem. 2002, 50, 3757.
[6] Yang, C.; Yang, S.; Song, B.-A.; Hu, D.-Y.; Chen, H.-J.; Xue, W.; Jin, L.-H.; Wu, J.; Xu, W.-M.; Bai, S. Chin. J. Org. Chem. 2010, 30, 1327 (in Chinese).
(杨超, 杨松, 宋宝安, 胡德禹, 陈红军, 薛伟, 金林红, 吴剑, 徐维明, 柏松, 有机化学, 2010, 30, 1327.)
[7] Song, X.-J.; Wang, F.-S.; Li, S.-R.; Hu, W.-B.; Wang, Y.-G. Chin. J. Org. Chem. 2011, 31, 572 (in Chinese).
(宋新建, 王发松, 李世荣, 胡卫兵, 汪焱钢, 有机化学, 2011, 31, 572.)
[8] An, Y.; Wei, W.; Mu, P.-P.; Jia, J.-Y.; Lü, J.-Z.; Chen, X. Chin. J. Org. Chem. 2010, 30, 1726 (in Chinese).
(安悦, 魏魏, 牟萍萍, 贾金英, 吕建洲, 陈欣, 有机化学, 2010, 30, 1726.)
[9] Terzioglu, N.; Gürsoy, A. Eur. J. Med. Chem. 2003, 38, 781.
[10] Dekhane, D. V.; Pawar, S. S.; Gupta, S.; Shingare, M. S.; Patil, C. R.; Thore, S. N. Bioorg. Med. Chem. Lett. 2011, 21, 6527.
[11] Mougenot, P.; Namane, C.; Fett, E.; Camy, F.; Dadji-Faïhun, R.; Langot, G.; Monseau, C.; Onofri, B.; Pacquet, F.; Pascal, C.; Crespin, O.; Ben-Hassine, M.; Ragot, J.-L.; Van-Pham, T.; Philippo, C.; Chatelsin-Egger, F.; Péron, P.; Bail, J. C. L.; Guillot, E.; Chsmiot-Clerc, P.; Chabanaud, M. A.; Pruniaux, M. P.; Schmidt, F.; Venier, O.; Nicolaï, E.; Viviani, F. Bioorg. Med. Chem. Lett. 2012, 22, 2497.
[12] Harish, K. P.; Mohana, K. N.; Mallesha, L. Russ. J. Bioorg. Chem. 2014, 40, 97.
[13] Li, Y.-J.; Yu, Y.; Jin, K.; Gao, L.-X.; Luo, T.-C.; Sheng, L.; Shao, X.; Li, J. Chin. J. Org. Chem. 2015, 35, 129 (in Chinese).
(李英俊, 于洋, 靳焜, 高立信, 罗潼川, 盛丽, 邵昕, 李佳, 有机化学, 2015, 35, 129.)
[14] Zai, W.-J.; Jiang, P.-P.; Loiseau, M. P.; Guo, H.-S.; Fan, X.-S. Chin. J. Org. Chem. 2015, 35, 1335 (in Chinese).
(宰文静, 将盼盼, 张新迎, Loiseau, M. P., 郭胜海, 范学森. 有机化学, 2015, 35, 1335.)
[15] Minni. P.; Abedelmajeed, N.; Dmitry, K.; Marcel, K.; Jari, Y.; Kirsi, O.; Reto, B.; Charles, L. J.; Vania, M. M.; Sami, A. J. Nat Prod. 2016, 79, 362.
[16] Yuan, X.-Y.; Zhang, L.; Han, X.-Q.; Zhou, Z.-Y.; Du, S.-J.; Wan, C.; Yang, D.-Y.; Tan, Z.-H. Chin. J. Org. Chem. 2014, 34, 170 (in Chinese).
(袁小勇, 张鹭, 韩小强, 周子原, 杜士杰, 万川, 杨冬燕, 覃兆海, 有机化学, 2014, 34, 170.)
[17] Li, S.; Jing, F.; Fu, X.-Y.; Zhao, J.-J.; Wang, X.-F.; Li, B.-L.; Liu, Y.-M.; Chen, B.-Q. Chin. J. Org. Chem. 2015, 35, 2624 (in Chinese).
(李莎, 荆芬, 付小云, 赵继军, 王雪峰, 李宝林, 刘玉明, 陈宝泉, 有机化学, 2015, 35, 2624.)
[18] Patel, H.; Mishra, L.; Noolvi, M.; Karpoormath, R.; Cameotra, S. S. Arch. Pharm. Chem. Life Sci. 2014, 347, 668.
[19] Zhang, Y. Ph.D. Dissertation, Nanjing Agricultural University, Nanjing, 2011 (in Chinese).
(张勇, 博士论文, 南京农业大学, 南京, 2011.)
[20] Shang, E.-C.; Liu, C.-L.; Du, Y.-J. Chem. Ind. Eng. Prog. 1995, 5, 8 (in Chinese).
(尚尔才, 刘长令, 杜英娟, 化工进展, 1995, 5, 8.)
[21] Wu, Q.; Song, B.-A.; Jin, L.-H.; Hu, D.-Y. Chin. J. Org. Chem. 2009, 29, 365 (in Chinese).
(吴琴, 宋宝安, 金林红, 胡德禹, 有机化学, 2009, 29, 365.)
[22] Bessard, Y.; Crettaz, Z. Tetrahedron 2000, 56, 4739.
[23] Xu, H.; Pan, W. H.; Song, D. D.; Yang, G. G. J. Agric. Food Chem. 2007, 55, 9351.
[24] Howe, K. R.; Shelton, R. B. J. Org. Chem. 1990, 55, 4603.
[25] Bai, S.-Z.; Lou, X.-H.; Yin, G.-L. Shanxi Chem. Ind. 2009, 29, 16 (in Chinese).
(白素贞, 娄新华, 尹桂玲, 山西化工, 2009, 29, 16.)
[26] Elway, A. H.; Abbas, A. A. Tetrahedron 2000, 56, 885
[27] Weng, J.-Q.; Liu, X.-H.; Huang, H.; Tan, C.-X.; Chen, J. Molecules 2012, 17, 989.
[28] Liu, G.; Liu, C.-P.; Ji, C.-N.; Sun, L.; Wen, Q.-W. Chin. J. Org. Chem. 2008, 28, 525 (in Chinese).
(刘刚, 刘春萍, 纪春暖, 孙琳, 温全武, 有机化学, 2008, 28, 525.)
[29] Bao, X.-P.; Liu, J.-H.; Zhang, F.; Zou, L.-B.; Jian, J.-Y. Chin. J. Synth. Chem. 2013, 21, 200 (in Chinese).
(鲍小平, 刘军虎, 张峰, 邹林波, 蹇军友, 合成化学, 2013, 21, 200.)
[30] Run, L.-L.; Fan, R.-J.; Liu, X.-H.; Weng, J.-Q. Chin. J. Org. Chem. 2015, 35, 1166 (in Chinese).
(阮铃莉, 范人杰, 刘幸海, 陈杰, 翁建全, 有机化学, 2015, 35, 1166.)
[31] Nikolas, F.; Charles, L. C.; Stephen, O. D.; Alexios, L. S.; David, E. W. J. Agric. Food Chem. 2006, 54, 1652.
[32] Juan, R. L.; Luis, J. C.; Fernando, A.; Luis, R. Mol. Pharm. 2010, 7, 1609.
[33] Goswami, S.; Jana, S.; Dey, S.; Adak, A. K. Aust. J. Chem. 2007, 60, 120.
[34] Zhang, G.; Gao, G.-Y.; Li, Q.-H.; Yang, X.-J. Chem. Reag. 2014, 36, 594 (in Chinese).
(张刚, 高光宇, 李清寒, 杨学军, 化学试剂, 2014, 36, 594.)
/
| 〈 |
|
〉 |
